Since the subject of this symposium is the relationship of Neuroscience with the fundamental notions of Psychoanalysis let us remind you what Sigmund Freud said at the beginning of the 20th century. In 1914 in his work "on Narcissism" he writes: "We must recollect that all of our provisional ideas in psychology will presumably one day be based on an organic substructure" Few years later, in his work "Beyond the Pleasure Principle" states again: " The deficiencies in our description would probably vanish if we were already in a position to replace the psychological terms with physiological or chemical ones…We may expect (physiology and chemistry) to give the most surprising information and we cannot guess what answers it will return in a few dozen years of questions we have put to it. They may be of a kind that will blow away the whole of our artificial structure of hypothesis"

We can see here how Freud, being an excellent neuroanatomist and a genuine son of the Enlightenment, questions his psychoanalytic theory.

Let us say that we are here in this meeting because we believe that psychoanalysis represents the most coherent and intellectually satisfying view of the mind. During the first half of the twentieth century, psychoanalysis revolutionized our understanding of mental life. It provided a remarkable set of new insights into unconscious mental processes, psychic determinism, and most importantly into the irrationality of human motivation. In the years following the World War II, in the 1950s and 1960s psychiatry abandoned its roots in biology and experimental medicine and evolved into a psychoanalytically based and socially oriented discipline that was surprisingly unconcerned with the brain as an organ of mental activity. Of course by merging the descriptive psychiatry of the period before World War II with psychoanalysis, psychiatry gained great deal in explanatory power and clinical insight. Unfortunately, this was achieved at the cost of weakening its ties with experimental medicine and with the rest of biology.

The drift away from biology was not simply due to changes in psychiatry,it was partly because of the slow maturation of the brain sciences. As Eric Kandel pointed out few years ago " in the late 1940s the biology of the brain was neither technically nor conceptually mature enough to deal effectively with the biology of most higher mental processes and their disorders. The thinking about the relationship between brain and behavior was dominated by a view that different mental functions could not be localized to specific brain regions. This view was espoused by Karl Lashley who argued that the cerebral cortex was equipotential: all higher mental functions were presumed to be represented diffusely throughout the cortex. To most psychiatrists and even to many biologists, the notion of the equipotentiality of the cerebral cortex made behavior seem intractable to empirical biological analysis".

In fact, the separation of psychiatry from biology had its origins even earlier. When Sigmund Freud first explored the implications of the unconscious mental processes to behavior, he tried to adopt a neural model of behavior in an attempt to develop a scientific psychology. I am talking about the "Project for a scientific psychology" . This book was written in 1895 few years after his magnificent publication on the structure of the neuronal cells. Freud was the first to show the fibrous morphology of the cytoplasm of the neuronal cells.

Before we proceed to a discussion of the "Project …" let us add the extremely interesting information for what we are discussing: in the same year, 1895, the founder of modern Neurobiology, Ramon Y Cajal published a book under the title "Algunas conjeturas sobre el mecanismo anatomico de la ideacion, association y attencion" (Conjections on the anatomical mechanisms of ideation, association and attention ). In this book Cajal, who, for some years was practising hypnosis for the treatment of hysteria suggests an anatomical model for the creation of ideas, of the association mechanisms and of the intentional actions. Similarly, Freud in his "Project…" suggests that brain functions are based on 3 systems:φ, ψ, and ω. The system φ consists of perception neurons which receive external stimuli through the form of energy that in order to reach the system is filtered by a specific filter. The system ψ is mainly psychic and receives internal stimuli which originate from instincts as it is sex and famine. In this system part of ego is also located. Finally, the system ω is a higher order system which integrates the information from systems ψ and φ and initiates the reaction of the motor system where the accumulated energy is discharged. Examining the Project using the recent neurobiological knowledge we can detect several aspects which keep their validity until today. For example Freud adopts the individual neurons theory connected to each other with synapses( contact barriers according to the terminology used by Freud). The individual neuron theory was advocated at that time by Ramon Y Cajal but until 1950ies it was not the predominant theory. Until 1950ies the predominant theory was the network theory, advocated by Golgi.

The " Project for a Scientific Psychology" was published several years after Freud’s death by Maria Bonaparte and his daughter Anne Freud.

Freud himself because of the immaturity of brain science at the time, abandoned this model for a pure mentalistic one based on verbal reports of subjective experiences. Initially, as again Eric Kandel has pointed out, this separation may have been as healthy for psychiatry as it was for psychology . It permitted the development of systematic definitions of behavior and disease that were not contingent on still-vague correlations with neural mechanisms . Moreover, by incorporating the deep concern of psychoanalysis for the integrity of an individual’s personal history , psychoanalytic psychiatry helped develop direct and respectful ways for physicians to interact with mentally ill patients, and it led to a less stigmatized social perspective on mental illness.

However, the initial separation of psychoanalysis from neural science advocated by Freud, was stimulated by the realization that a merger was premature. But as psychoanalysis evolved after Freud, rather than being seen as premature, the merger of psychoanalysis and neuroscience was seen as unnecessary, because neural science was increasingly considered irrelevant.

However, again, many years have passed and brain science today is in the cusp of a revolution similar to the unraveling of the human genome in 1990s. Terms like consciousness or unconscious can be discussed not only on a psychological or psychoanalytic basis but also on a neurobiological one. Of course the subject of this presentation is the "unconscious" however let us say few words about consciousness. According to several investigators, consciousness is distinguished in primary and higher order consciousness. Primary consciousness contains the state of being aware of things in the world ,of having mental images of the present. Higher order consciousness includes recognition by a thinking agent of his actions or his emotions. It embodies a model of his personality, in his past, his future, as well as in his present. Gerald Edelman in his book "Bright Air, Brilliant Fire" suggests a model for primary consciousness very similar to the model that Freud suggested in his "Project…" . According to Edelman, past signals related to values (set by internal control systems, self for Edelmsan, system ψ for Freud) and categorized signals from outside world (nonself for Edelman, system φ for Freud) are correlated and lead to memory in conceptual areas (system ω for Freud). This memory, which is capable for conceptual categorization, is linked by reentrant paths to current perceptual categorization of world signals. This results in primary consciousness. The difference between Freud’s and Edelman’s system is that in Edelman’s system due to the progress of brain research, the function of specific brain regions like Hippocampus, Amygdala or Septum are incorporated in the model. This was impossible at the end of the 19th century when Freud wrote his "Project…"

Although Aristotle in the ancient years and Leibnitz, Immanuel Kant, Herbart or von Helmholtz referred to unconscious processes, it was Sigmund Freud who really pointed up and established the role of unconscious in our behavior and feelings.The postulation of an unconscious is a central principle of Freud’s psychological theories.Before proceeding to a further discussion on unconscious processes let us explain, for those who are not familiar, the terms of explicit or declarative and implicit or procedural memory.

Explicit or declarative memory encodes information about autobiographical events as well as factual knowledge. Its information depends on cognitive processes such as evaluation, comparison and inference. Explicit memories can be recalled by a deliberate act of recollecting. They are sometimes established in a single trial or experience, and often can be concisely expressed in declarative statements, such as " Yesterday I went to the Ancient Theater of Patras where the National Orchestra and the Chorus of the National Opera played Beethoven’s 9th Symphony" (autobiographical event), or "Gold is heavier than the water" (factual event).

Implicit or procedural memory has an automatic or reflexive quality, and its formation and recall are not absolutely dependent on awareness or cognitive processes.

It remains in an unconscious level. This type of memory accumulates slowly through repetition over many trials, is expressed primarily by improved performance, and cannot ordinarily be expressed in words. Implicit memory is not a single memory system but a collection of processes involving several different brain systems that lie deep within the cerebral cortex. For example, as we will see later on, the association of feelings, such as fear, with events involves a structure called the amygdala .

Sigmund Freud maintained that the therapeutic effect of psychoanalysis was mainly linked to a process of reconstruction achieved by work on the patient’s autobiographic memory. In other words, the very concept of the psychoanalytic process is to recover repressed, from explicit memory , experiences ( we could call this de-repression) overcoming of course the patients resistance.

On the other hand, according to Eric Kandel the notion of unconscious mental functions is not only interesting itself, but it also plays an extremely important role in our attempt to understand psychic determinism. He says that part of our unconscious ego, that he names procedural unconscious, has not been repressed and is concerned with unconscious habits, and perceptual and motor skills that are mapped into procedural (implicit) memory. Many changes that take place during psychoanalysis concern precisely this very part of the unconscious. This progress does not depend on conscious awareness of the repressed unconsciousness as Sigmund Freud suggested. It does not, in other words, require the unconscious to be transported into the realm of the conscious. It consists, rather, of changes in behavior that increase the range of the subject’s procedural strategies for doing and being. Here Eric Kandel mentions Marianne Goldberg who claims that generally people do not remember, in any conscious way, the circumstances under which they assimilated the moral rules that govern their behavior.

Similarly, Otto Kernberg, Professor of Psychiatry and Psychoanalysis at the Universities Cornell and Columbia suggests: " One other implication of these formulations is that the deepest layers of psychic experience that will organize the psychic apparatus are represented by peak affect states of a positive or negative quality, in the context of which the deepest aspects of the relationships between self and others are internalized, presumably at first into procedural memory, and only later on in the form of declarative or preconscious memory"

Also, Mauro Manzia, Professor of Neurophysiology and Psychoanalyst at the University of Milan talking about the early experiences indicates that: "these experiences, with the fantasies and defenses they induce, cannot be repressed because the structures of the explicit memory needed for repression take two or three years to mature. Therefore, in these preverbal and presymbolic stages of life, when the child and its mother identify with each other, with proto-linguistic forms of communication shared affective states and a relation in which intersubjectivity implies "inter-fantasy" the infant will be able to create affective representations and store them in the implicit memory. These will form the unconscious, unrepressed structure of his mind" Therefore "a critical part of the psychoanalysts work today involves transforming symbolically and rendering verbalizable the implicit structures in the patient’s mind that mark the unrepressed unconscious".

Furthermore, Louis Sanders, Daniel Stern and their colleagues in Boston have developed the idea that during the analysis there are moments of meaning-moments in the interaction between patient and therapist-which represent the achievement of a new set of implicit memories that permits the therapeutic relationship to progress to a new level. This progression does not depend on conscious insights; it does not require, so to speak, the unconscious becoming conscious.

Although the objectives of the Boston Group and of Mauro Mancia differ substantially, these four examples indicate that several investigators from the fields of both Neuroscience and Psychoanalysis believe that implicit or procedural unrepressed memories play a very crucial role in the formation of the unconscious ego and that many changes that occur during the psychoanalytic procedure concern this part of the unconscious.

Let us consider now two examples in order to indicate how those unconscious implicit memories can be established and how this unconscious part of our memory can affect consciousness.

A number of different experiments suggest that neurons in the amygdala a brain region located under the temporal lobe can memorize stimuli associated with pain. In an experiment, rabbits were trained to associate the sound of a tone with mild pain. A typical Pavlovian experiment. The researchers made use of the fact that a characteristic sign of fear in rabbits is a change in heart rate. Animals were placed in a cage, and at various times they heard one of two tones. One tone was followed by a mild electrical shock to the feet through the metal floor of the cage, the other tone was benign. After training, it was found that the rabbit’s heart rate developed a fearful response to the tone associated with pain, but not to the benign tone. Prior to training, neurons in the central nucleus of the amygdala failed to respond to the tones used in the experiment. However, after training, neurons in the central nucleus responded to the shock-related tone but not to the benign one. Joseph LeDoux of New York University has shown that after this type of fear conditioning, amygdala lesions eliminate the learned visceral responses, such as the changes in heart rate and blood pressure. Joseph LeDoux proposed the following circuit to account for learned fear. Auditory information is sent to the basolateral region of the amygdala, where cells in turn send axons to the central nucleus. Afferents from the central nucleus project to the hypothalamus, which can alter the state of the ANS, and to the periaqueductal gray matter in the brain stem, which can evoke behavioral reactions via the somatic motor system. The emotional experience is thought to be based on activity in the cerebral cortex.

Thus amygdala can induce fear and anxiety responses not only in the presence of a painful stimulus induced by an associated stimulus. Central nucleus also projects to cortical association areas and this pathway is important for the perception of the emotional experience. A component of both primary and higher order consciousness. However, this experience has to be distinguished from what is happening inside the central nucleus. The memory that is established there, the cause of autonomic, motor and conscious reactions, does not reach the level of the explicit (declarative) memory, it is an unconscious, implicit (procedural) memory. An unconscious but not repressed memory.

The second example that we would like to present is the following. It is well known that contrary to the eyes, the location of a sound source does not project directly to the sensory surface of the ear. Superior colliculus, a brain region in which both visual and auditory stimuli converge, contains spatial sensory maps that are aligned to each other with the superficial layers being visual and the deeper layers being multimodal. During development, as Irini Skaliora has shown, vision calibrates the spatial tuning of auditory neurons in the deep layers of Superior Colliculus. Auditory orienting behavior and auditory spatial tuning are adjusted adaptively in response to optical displacement of the visual field. For example, owls reared with horizontally displacing prisms during a critical period of development exhibit a horizontal shift of the auditory receptive fields. If the prisms are removed within the critical period auditory tuning returns to normal. However , re-exposure to the prisms as adults, resulted in the re-expression of the adaptive responses that had been memorized (and forgotten) during the critical period. Of course, this type of memory is an implicit memory.

In conclusion, we can say that experience during the early sensitive period not only shapes auditory space processing, but also expands the capacity of experience-driven changes in the adulthood.. This type of results support in terms of biology the psychoanalytic ideas suggesting that experiences and forgotten (we use this term instead of repressed) adaptive responses of the early sensitive periods of life have the capacity to affect experience-driven responses in adulthood.

Yes, we feel your objections, what are you talking about in such a naïve way, owls and rabbits are not humans. What we are trying to do, is to present data showing the brain mechanisms that are behind the unconscious processes and how these processes affect consciousness. But let us close this presentation by discussing a very interesting work on unconscious and conscious perception of fear by human volunteers. Eric Kandel and his M.D-Ph.D student Amit Etkin produced conscious perception of fear by presenting fearful faces for long period, so people had time to reflect on them. They produced unconscious perception of fear by presenting the same faces so rapidly that the volunteers were unable to report which type of expression they had seen. They were not even sure they had seen a face. Since even normal people differ in their sensitivity to a threat, they gave all of the volunteers a questionnaire designed to measure background anxiety. Not surprisingly, when they showed the volunteers pictures of faces with fearful expression, they found prominent activity in the amygdala. But what was surprising was that conscious and unconscious stimuli affected different regions of the amygdala, and they did so to differing degrees in different people, depending on their baseline anxiety. Unconscious perception of fearful faces activated the basolateral nucleus. Activation of this nucleus by unconscious perception of fearful faces occurred in direct proportion to a person’s background anxiety: the higher the measure of background anxiety the greater the person’s response. People with low background anxiety had no response at all. Conscious perception of fearful faces, in contrast, activated the dorsal region of amygdala, and it did so regardless of a person’s background anxiety. These results confirm biologically the importance of the psychoanalytic idea of unconscious emotion. They suggest, that the effects of anxiety are exerted most dramatically in the brain when stimulus is left to imagination rather than when it is perceived consciously. Once the image of a frightened face is confronted consciously, even anxious people can accurately appraise whether it truly poses a threat.

Eric Kandel discussing these data in his very recent book titled "In Search of Memory" writes: "A century after Freud suggested that psychopathology arises from conflict occurring on an unconscious level and that it can be regulated if the source of the conflict is confronted consciously, our imaging studies suggest ways in which such conflicting processes may be mediated in the brain. Moreover, the discovery of a correlation between volunteers background anxiety and their unconscious mental processes are part of the brain’s system of information processing".

Here Eric Kandel lays a strong bridge between Psychoanalysis and Neuroscience. Let us hope that gradually more and more psychoanalysts and neuroscientist will join him. This meeting is a step towards that direction.